rs150064711

Variant names:

• chr10-133556759-G-A
• rs150064711
• NM_001143764.3:c.528C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-133556759-G-A
• chr10-133556759-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_001143764.3(SYCE1):​c.528C>T​(p.His176His) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,562,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00026 (0 hom.)
• Consequence: SYCE1 NM_001143764.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.0001626
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.52
• Publications: 1 publications found

Genes affected

SYCE1 (HGNC:28852): (synaptonemal complex central element protein 1) This gene encodes a member of the synaptonemal complex, which links homologous chromosomes during prophase I of meiosis. The tripartite structure of the complex is highly conserved amongst metazoans. It consists of two lateral elements and a central region formed by transverse elements and a central element. The protein encoded by this gene localizes to the central element and is required for initiation and elongation of the synapsis. Allelic variants of this gene have been associated with premature ovarian failure and spermatogenic failure. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

CYP2E1 (HGNC:2631): (cytochrome P450 family 2 subfamily E member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is induced by ethanol, the diabetic state, and starvation. The enzyme metabolizes both endogenous substrates, such as ethanol, acetone, and acetal, as well as exogenous substrates including benzene, carbon tetrachloride, ethylene glycol, and nitrosamines which are premutagens found in cigarette smoke. Due to its many substrates, this enzyme may be involved in such varied processes as gluconeogenesis, hepatic cirrhosis, diabetes, and cancer. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-133556759-G-A is Benign according to our data. Variant chr10-133556759-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3058525.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.52 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143764.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYCE1	NM_001143764.3	MANE Select	c.528C>T	p.His176His	splice_region synonymous	Exon 8 of 13	NP_001137236.1	Q8N0S2-1
	SYCE1	NM_001143763.2		c.528C>T	p.His176His	splice_region synonymous	Exon 8 of 13	NP_001137235.1	A0A0B4J1R9
	SYCE1	NM_130784.4		c.420C>T	p.His140His	splice_region synonymous	Exon 8 of 13	NP_570140.1	Q8N0S2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYCE1	ENST00000343131.7	TSL:1 MANE Select	c.528C>T	p.His176His	splice_region synonymous	Exon 8 of 13	ENSP00000341282.5	Q8N0S2-1
	SYCE1	ENST00000303903.10	TSL:1	c.528C>T	p.His176His	splice_region synonymous	Exon 8 of 13	ENSP00000303978.5	A0A0B4J1R9
	CYP2E1	ENST00000368520.1	TSL:1	n.3457G>A		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152160 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000207 AC: 36 AN: 173912 AF XY: 0.000185

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000541

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000295

Gnomad OTH exome AF: 0.000207

GnomAD4 exome AF: 0.000264 AC: 372 AN: 1410170 Hom.: 0 Cov.: 31 AF XY: 0.000251 AC XY: 175 AN XY: 696766

African (AFR) AF: 0.00 AC: 0 AN: 31998

American (AMR) AF: 0.000491 AC: 18 AN: 36676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25286

East Asian (EAS) AF: 0.00 AC: 0 AN: 36244

South Asian (SAS) AF: 0.00 AC: 0 AN: 80150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.000315 AC: 342 AN: 1085308

Other (OTH) AF: 0.000205 AC: 12 AN: 58562

GnomAD4 genome AF: 0.000144 AC: 22 AN: 152278 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74470

African (AFR) AF: 0.0000963 AC: 4 AN: 41548

American (AMR) AF: 0.000327 AC: 5 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000209 Hom.: 0

Bravo AF: 0.000204

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SYCE1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.0
DANN	Benign	0.81
PhyloP100		-1.5

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.078
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs150064711; hg19: chr10-135370263; COSMIC: COSV100385641;